The fact that the PPAR-α agonist WY14643 did not alter the interoceptive effects of nicotine in the drug-discrimination procedure is consistent with previous findings that nicotine's reward-related dopaminergic effects are not well-captured by this procedure (32). For example, even though the cannabinoid CB1 receptor antagonist rimonabant can block nicotine reward (i.e., self-administration, conditioned place preference) and nicotine-induced increases of dopamine levels in the nucleus accumbens, rimonabant does not alter nicotine discrimination (26,33). Similarly, the dopamine D3 antagonist BP897 blocks nicotine-induced conditioned place preference, but does not alter nicotine discrimination (34). The finding that WY14643 blocked nicotine's effects on dopamine but did not alter its discriminative effects is consistent with previous data suggesting that nicotine discrimination can be mediated by nicotine's indirect effects on serotonin, cannabinoid, and glutamate receptors (35).
